GSK and Medicines for Malaria Venture (MMV) today announced the publication of positive results from two phase III studies of single-dose tafenoquine for the radical cure (prevention of relapse) of Plasmodium vivax (P. vivax) malaria in The New England Journal of Medicine.

Headline results from the DETECTIVE and GATHER studies, part of a comprehensive global P. vivax radical cure clinical development programme, were announced in June 2017. The results supported the approval of single-dose (1-day) tafenoquine by the U.S. Food and Drug Administration (FDA) in July 2018 (Krintafel) and the Australian Therapeutic Goods Administration (TGA) in September 2018 (Kozenis) for the radical cure of P. vivax malaria, a disease that is estimated to cause around 7.5 million clinical infections every year. The existing standard of care, primaquine, must be taken for 14 days making compliance often low in endemic settings.

The DETECTIVE study, conducted in 522 patients investigated a 1-day course of tafenoquine (300mg), a 14-day course of primaquine (15mg), or placebo, with all patients also receiving a 3-day course of chloroquine to treat clinical symptoms, met its primary endpoint.1

Using a confirmed FDA-preferred analysis (Kaplan Meier analysis), a significantly greater proportion of patients in the tafenoquine group remained relapse-free over the 6-month follow-up period compared with patients in the placebo group (62.4% vs 27.7%), with an odds ratio of 0.3, p<0.001. Further, a significantly greater proportion of patients in the primaquine group were relapse-free over the 6-month follow-up period compared with patients on placebo (69.6% vs 27.7%), with an odds ratio of 0.26, p<0.001. High compliance with primaquine treatment of greater than 95% was observed in this controlled clinical setting.

Adverse events from the study were consistent with the known safety profile of tafenoquine. Mild, asymptomatic declines in haemoglobin (a protein in red blood cells that carries oxygen) were observed more frequently in patients taking tafenoquine, and all recovered without intervention. The proportion of patients experiencing adverse events (AEs) in the first 29-days during the 6-month study was similar for each treatment group; the frequency was 48.8% for tafenoquine, 46.5% for primaquine, and 48.9% for placebo. The frequency of serious AEs was 8.1% for tafenoquine (n=21, 14 of which were due to decline in haemoglobin that were all mild to moderate in severity and all recovered without specific medical intervention), 3.1% (n=4) for primaquine and, 4.5% (n=6) for placebo.

The GATHER study, conducted in 251 patients, investigated the effect of a single-dose of tafenoquine (300mg) on levels of haemoglobin when compared to a 14-day course of primaquine (15mg), with all patients also receiving a standard 3-day course of chloroquine.2

The incidence of decline in haemoglobin (the primary endpoint) was very low and similar between the two treatment groups (2.4% for patients receiving tafenoquine 1.2% for patients receiving primaquine), with the difference in proportions (95% CI) of 1.23% (-4.16%, 4.98%).

The frequency of adverse events was 72% for the tafenoquine group and 75% for the primaquine group and the frequency of serious adverse events was 4% for the tafenoquine group and 1% for the primaquine group.

The regulatory approvals of tafenoquine by the FDA and TGA will be informative to regulatory agencies in malaria-endemic countries.Tafenoquine will be provided at an affordable price to maximise access of the medicine to those who need it most.

Dr. Hal Barron, Chief Scientific Officer and President of Research and Development, GSK, said: “Treating Plasmodium vivax malaria is particularly challenging because the parasite has the ability to lie dormant in the liver resulting in relapses. Poor compliance to primaquine treatment in real-world settings can lead to higher relapse rates than those seen in the controlled setting of clinical trials, so a single-dose treatment with tafenoquine is an attractive proposition. We are pleased to have the results of these pivotal studies published today, and look forward to progressing further regulatory filings of tafenoquine in P. vixax endemic countries.”

Dr. David Reddy, Chief Executive Officer of MMV said: “Without treatment to stop the relapse of P. vivax, infected patients live with the constant threat of malarial symptoms returning without warning. MMV and GSK, long-standing partners in the fight against malaria, developed tafenoquine to help put a stop to the relapse. We are delighted to see the results of the phase III studies published in the NEJM. These positive results demonstrate the efficacy and safety of tafenoquine in an unprecedented single-dose for relapsing malaria, potentially offering countries a new tool as they strive towards malaria elimination.”